Parasiticidal formulation and a method of making this formulation

ABSTRACT

A parasiticidal formulation is provided. This formulation includes a pyrrolidone solvent, a bridging solvent, and an parasiticidal agent. One or more parasiticidal agents may be included in the formulation. Preferably, the formulation contains both closantel and ivermectin. Another aspect of the present invention is a method of making this parasiticidal formulation. This method includes mixing a pyrrolidone solvent and a bridging solvent to form a solvent solution and adding one or more parasiticidal agents to the solvent solution. A further aspect of the present invention is a method for administering the parasiticidal formulation of the present invention to an animal. This method of administration includes providing the parasiticidal formulation described above and applying this formulation to the skin of an animal, wherein the formulation is absorbed through the animal&#39;s skin.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0001] Not applicable.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] Not applicable.

BACKGROUND OF THE INVENTION

[0003] The present invention relates to a parasiticidal formulation anda method for making the formulation. More specifically, the presentinvention relates to a parasiticidal formulation for use in veterinaryapplications.

[0004] Currently, closantel, a parasiticidal agent, is available in aninjectable form or as an oral drench. One disadvantage with theseclosantel parasiticidal formulations is that they are not available in apour-on form.

[0005] Ivermectin, another parasiticidal agent which kills differentparasites from closantel, may be purchased in an injectable form, as apour-on formulation, in a paste form, as an oral drench, or in achewable form. The ivermectin injectable formulations currentlyavailable contain glycerol formal or propylene glycol to dissolve theivermectin. The ivermectin pour-on formulations currently availablecontain isopropyl alcohol or a mixture of caprylic acids and caprylicesters to dissolve the ivermectin.

[0006] One disadvantage with both injectable and pour-on ivermectinformulations currently available is that none of these formulations willdissolve closantel and like parasiticidal formulations in concentrationssufficient to be useful. Another disadvantage with the ivermectinpour-on formulations available is that they only have up to a 0.5%weight per volume (w/v) concentration of ivermectin.

[0007] Additionally, a disadvantage with parasiticidal formulationscurrently available is that closantel and ivermectin are not availablein a single formulation, and therefore a broadened spectrum of parasiteprotection is not available in a single formulation. Still further,parasiticidal agents, including, but not limited to closantel andivermectin, cannot be combined in pour-on formulations currentlyavailable in a manner that keeps both parasiticidal agents in solution.

[0008] In order to overcome these disadvantages, a parasiticidalformulation containing an effective solvent delivery system that allowsone or more parasiticidal agents to dissolve, especially closantel andivermectin in combination, is needed. In addition, the resultingparasiticidal formulation should be usable in a pour-on or an injectableform. Still further, the solvent delivery system should be able to holdlarger amounts of parasiticidal agents than prior formulations.

SUMMARY OF THE INVENTION

[0009] It is an object of the present invention to provide aparasiticidal formulation containing more than one parasiticidal agentor a larger amount of a single parasiticidal agent than conventionalformulations that may be a administered as a pour-on product in order tofacilitate easier administration of the parasiticidal formulation.

[0010] It is another object of the present invention to provide aparasiticidal formulation that contains at least two differentparasiticidal agents so as to obtain a broadened spectrum of parasiteprotection.

[0011] It is a further object of the present invention to provide amethod of making a parasiticidal formulation that achieves the foregoingobjects.

[0012] Still another object of the present invention is to provide amethod for administering a parasiticidal formulation that achieves theforegoing objects.

[0013] According to the present invention, the foregoing and otherobjects are achieved by a pour-on or an injectable parasiticidalformulation that includes a mixture of a pyrrolidone solvent, a bridgingsolvent and at least one parasiticidal agent. One or more parasiticidalagents may be included in the formulation. Preferably, the formulationcontains both closantel and ivermectin. Another aspect of the presentinvention is a method of making this parasiticidal formulation. Thismethod includes mixing a pyrrolidone solvent and a bridging solvent toform a solvent solution and adding one or more parasiticidal agents tothe solvent solution. A further aspect of the present invention is amethod for administering the parasiticidal formulation of the presentinvention to an animal. This method of administration includes providingthe parasiticidal formulation described above and applying thisformulation to the skin of an animal, wherein the formulation may beabsorbed through the animal's skin.

[0014] Additional objects, advantages and novel features of theinvention will be set forth in part in the description which follows,and in part will become apparent to those skilled in the art uponexamination of the following, or may be learned from the practice of theinvention. The objects and advantages of the invention may be realizedand attained by means of the instrumentalities and combinationsparticularly pointed out in the appended claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0015] The parasiticidal formulation of the present invention is aneffective pour-on or injectable formulation for protection againstparasites. The formulation includes a solvent delivery system and one ormore parasiticidal agents. The solvent delivery system includes amixture of a pyrrolidone solvent and a bridging solvent. This mixtureprovides a unique solvent system which allows one or more parasiticidalagents to dissolve effectively when added to the solvents.

[0016] The pyrrolidone solvent that may be used in the formulation ofthe present invention includes, but is not limited to,N-methyl-2-pyrrolidone, 2-pyrrolidone, N,5-dimethyl-2-pyrrolidone,3,3-dimethyl-2-pyrrolidone, N-ethyl-2-pyrrolidone,N-ethoxy-2-pyrrolidone, N-ethylene-2-pyrrolidone, 1-pyrrolidone, or anycombinations thereof. Preferably, the pyrrolidone solvent isN-methyl-2-pyrrolidone or 2-pyrrolidone. The pyrrolidone solventdesirably is present in the solvent delivery system in an amounteffective, in combination with a bridging solvent, for dissolving atherapeutic amount of one or more parasiticidal agents.

[0017] The bridging solvent that may be used in the formulation of thepresent invention includes, but is not limited to, diethylene glycolmonobutyl ether (DGME), benzyl benzoate, isopropyl alcohol, xylenes, orany combinations thereof. If xylenes are used, usually a combination ofortho-xylene, meta-xylene and para-xylene is used. The bridging solventaids in dissolving the parasiticidal agents and acts to carry theformulation through an animal's skin once it is applied to the skin. If2-pyrrolidone is used as the pyrrolidone solvent, then preferablyxylenes are used as the bridging solvent. If a pyrrolidone solvent otherthan 2-pyrrolidone is used, then the preferred bridging solvent is DGME.In any event, the solvent delivery system must include an amount of thebridging solvent that is effective, in combination with the pyrrolidonesolvent, to dissolve a therapeutic amount of the active parasiticidalagent or agents.

[0018] The combination of a pyrrolidone solvent and a bridging solventto form the unique solvent delivery system of the present inventionallows one or more parasiticidal agents to dissolve. The solvent systemdissolves the parasiticidal agents and keeps them in solution. Thesolvent delivery system also functions to transport one or moreparasiticidal agents into an animal so that the agent or agents mayinteract therapeutically with parasites in the animal.

[0019] The parasiticidal agents that may be used in the formulation ofthe present invention include, but are not limited to, closantel,oxyclozanide, praziquantel, pyrantels, tetrahydropyrimidines,probenzimidazoles, imidazothiazoles, macrocyclic lactones,benzimadizoles, tetramisoles, avermectins, epsiprantel, morantel,febantel, netobimin, clorsulon, bunamidine, nitroscanate, melarsomine,amidines, benzoyl urea derivatives, carbamates, nitroquanidines,pyrazoles, pyrethrins, pyrethroids, pyriproxyfen, acylhydrazones and anycombinations thereof.

[0020] An example of a pyrantel that may be used is pyrantel pamoate.Examples of benzimadizoles that may be used include, but are not limitedto, mebendazole, oxibendazole, fenbendazole, oxfendazole,triclabendazole, flubendazole, ricobendazole, thiabendazole, andalbendazole. Preferably, if a tetramisole is used, it is levamisole.Examples of avermectins that may be used include, but are not limitedto, ivermectin, moxidectin, doramectin, eprinomectin, and milbemycin.Preferably, a combination of ivermectin and closantel is used as theparasiticidal agent in the formulation. Ivermectin kills a variety ofinternal and external parasites; a number of worms including stomachworms, intestinal worms, lungworms, barber's pole worms, lice, andmites. Closantel kills adult and immature barber's pole worms, liverflukes, and all stages of nasal bot in sheep. Most preferably, theformulation contains ivermectin and closantel in about a 1:10 ratio.

[0021] As discussed above, closantel and ivermectin each provideprotection against different species of parasites. Thus, when closanteland ivermectin are combined in a single parasiticidal formulation, theformulation provides protection against a broader spectrum of parasitesthan a formulation containing either parasiticidal agent alone.Additionally, because the solvent delivery system of the presentinvention effectively dissolves both closantel and ivermectin, if eitheractive ingredient is used in the absence of the other, the solventdelivery system of the present invention may still be used. When usedwith a single parasiticidal agent, including, but not limited toivermectin or closantel, the solvent delivery system of the presentinvention may allow the parasiticidal agent to dissolve at a higherconcentration than formulations currently available. For example, anivermectin formulation with a concentration of ivermectin from about1-5% w/v or higher may be made. Thus, the solvent delivery system of thepresent invention allows for several formulations, each manufactured toprovide protection against a targeted parasite population.

[0022] The preferred total amount of parasiticidal agent in theformulation of the present invention may be about 0.1-15% w/v, whetherused singularly or in combination. Preferably, the formulation of thepresent invention includes about 1-8% w/v parasiticidal agent.

[0023] When using closantel and ivermectin in combination, theparasiticidal formulation of the present invention preferably mayinclude about 1-10% w/v closantel and about 0.1-5% w/v ivermectin. Morepreferably, the formulation of the present invention may include about3-7% w/v closantel and about 0.3-0.7% w/v ivermectin. Most preferably,the formulation of the present invention may include about 5% w/vclosantel and about 0.5% w/v ivermectin.

[0024] If the chosen pyrrolidone solvent is N-methyl-2-pyrrolidone, theparasiticidal formulation of the present invention preferably mayinclude about 5-90% w/v N-methyl-2-pyrrolidone. More preferably, itincludes about 30-50% w/v N-methyl-2-pyrrolidone. Most preferably, itmay include about 40-45% w/v N-methyl-2-pyrrolidone. However, whenincreased amounts of closantel are used in the formulation, the amountof N-methyl-2-pyrrolidone may also be increased to ensure that theclosantel dissolves. Thus, amounts at the higher ends of the rangesgiven are used.

[0025] If the chosen pyrrolidone solvent is 2-pyrrolidone, theparasiticidal formulation of the present invention preferably mayinclude about 15-90% w/v 2-pyrrolidone. More preferably, it may includeabout 50-80% w/v 2-pyrrolidone. Most preferably, it may include about70% w/v 2-pyrrolidone.

[0026] If any pyrrolidone solvent other than N-methyl-2-pyrrolidone or2-pyrrolidone is chosen, the parasiticidal formulation of the presentinvention preferably may include about 10-90% w/v pyrrolidone solvent.More preferably, it may include about 30-70% w/v pyrrolidone solvent.

[0027] If the chosen bridging solvent is DGME, the parasiticidalformulation of the present invention may preferably include about 10-90%w/v DGME. More preferably, it may include about 25-75% w/v DGME. Mostpreferably, it may include about 50% w/v DGME. If any bridging solventother than DGME is chosen, either singularly or in combination, theparasiticidal formulation of the present invention preferably mayinclude about 10-90% w/v bridging solvent. More preferably, it mayinclude about 30-70% w/v bridging solvent. Most preferably, it mayinclude about 50% w/v bridging solvent.

[0028] While the solvent delivery system and a parasiticidal agent arethe only components necessary in the formulation of the presentinvention, a number of optional ingredients may be added to enhancecertain properties of the formulation. One such optional ingredient is astabilizer which acts to enhance the stability of the parasiticidalformulation. Stabilizers that may be used in the formulation of thepresent invention include, but are not limited to, vitamin B₁₂, vitaminE acetate, niacinamide, ascorbic acid, butylated hydroxyaniline,thioctic acid, sorbic acid, sodium formaldehyde sulfoxylate, butylatedhydroxytoluene, or any combinations thereof. Preferably, vitamin B₁₂ andvitamin E acetate, either singularly or in combination, are used asstabilizers in the formulation of the present invention because they arethe most effective in preserving the active ingredients.

[0029] If vitamin B₁₂ is chosen as a stabilizer for the formulation, theparasiticidal formulation of the present invention preferably mayinclude about 0.005-1% w/v vitamin B₁₂. More preferably, it may includeabout 0.01-0.5% w/v vitamin B₁₂. Most preferably, it may include about0.1% w/v vitamin B₁₂.

[0030] If vitamin E acetate is chosen as a stabilizer for theformulation, the parasiticidal formulation of the present inventionpreferably may include about 0.05-5% w/v vitamin E acetate. Morepreferably, it may include about 0.5-1.5% w/v vitamin E acetate. Mostpreferably, it may include about 1% w/v vitamin E acetate.

[0031] If any stabilizer other than vitamin B₁₂ or vitamin E acetate isused in the formulation, the formulation of the present inventionpreferably may include about 0.005%-15% w/v stabilizer. More preferably,it may include about 0.05-3% w/v stabilizer. These ranges of stabilizersalso may apply if two or more of the stabilizers are used incombination, such as when vitamin B₁₂ and vitamin E acetate are used incombination.

[0032] Another optional ingredient that may be included in theformulation of the present invention is a solubility agent. Solubilityagents of the present invention may include, but are not limited to,mixtures of caprylic acids and esters, ethyl oleate, propylene glycol,Arachis oil (peanut oil), or any combinations thereof. The mixtures ofcaprylic acids and esters may contain from about 99% acids to about 99%esters. Solubility agents aid in dissolving the active ingredients ofthe formulation, but also aid in spreading the formulation across ananimal's skin once it has been poured over the skin, making theformulation less aggressive to the skin. Still further, because each ofthese solubility agents are oily substances used in the formulation,they help the skin retain moisture.

[0033] The parasiticidal formulation of the present invention preferablymay include about 5-50% w/v solubility agent. More preferably, theformulation of the present invention may include about 10-35% w/vsolubility agent. Most preferably, the formulation of the presentinvention may include about 20% w/v solubility agent.

[0034] Another ingredient that optionally may be added to theformulation of the present invention is a colorant. Colorants give theformulation a more consistent color and aid an observer in determiningwhat areas of an animal's skin have been treated. A colorant may beadded to the parasiticidal formulation of the present invention in anamount sufficient that the formulation poured onto the animal's skin canbe seen. In addition, water may be added to the formulation of thepresent invention. In fact, it may be necessary to add water to theformulation if a colorant is added so that the colorant is adequatelydispersed. Further, a pH stabilizer may be added to the parasiticidalformulation of the present invention to prevent hydrolysis. Examples ofpH stabilizers that may be used in conjunction with the presentinvention include, but are not limited to, triethanolamine anddiethanolamine.

[0035] One preferred formulation of the present invention includesN-methyl-2-pyrrolidone, DGME, closantel, and ivermectin. Anotherpreferred formulation of the present invention includes 2-pyrrolidone,xylenes, closantel, and ivermectin. A highly preferred formulation ofthe present invention is described in Example 1.

[0036] The parasiticidal formulation of the present invention is made bycombining a pyrrolidone solvent, a bridging solvent, and one or moreparasiticidal agents to form a mixture. Preferably, closantel andivermectin may be used in combination as the parasiticidal agents. Theorder in which components are added in making the formulation is notcritical. The formulation may optionally be heated to between about 40°and 80° C. continuously or intermittently during its preparation inorder to dissolve the components more quickly. If vitamin B₁₂is used asa stabilizer, it is recommended that the formulation may be heated toabout 50° C. prior to adding the vitamin B₁₂. Preferably, a portion ofthe pyrrolidone solvent, the bridging solvent, or the solubility agentmay be added last so that a specific quantity of parasiticidalformulation may be obtained and to ensure that all ingredients dissolve.This process can be scaled to make any desired quantity of theformulation.

[0037] One preferred method of making the parasiticidal formulation ofthe present invention includes placing a quantity of pyrrolidone solventin a vessel and warming it to about 50° C. Next, a stabilizer is added,and the resulting solution is cooled to room temperature. The bridgingsolvent is then added and mixed into the solution for an effectiveperiod of time. Optionally, a second stabilizer may then be added andmixed until all ingredients are adequately dissolved. Following this,ivermectin is added and mixed into the solution until it is dissolved.Closantel is then added, and the mixture is agitated until a portion ofthe closantel is dissolved. The closantel likely will not completelydissolve. Thus, it will be necessary to add an additional portion ofpyrrolidone solvent to ensure that all components adequately dissolve.

[0038] The parasiticidal formulation of the present invention may beadministered as a pour-on product or as an injectable formulation to anyanimal. Preferably, it is administered as a pour-on product. It isespecially useful for cattle, horses, sheep, goats, and pigs. Mostpreferably, it is administered to cattle. It may be poured over ananimal's back or may be poured on any other body part of an animal thatneeds treatment. Preferably, it may be administered in a dosage of about0.02-0.4 milliliters of formulation per kilogram of animal. Morepreferably, it may be administered in a dosage of about 0.02-0.3milliliters of formulation per kilogram of animal. Most preferably, itmay be administered in a dosage of about 0.02-0.25 milliliters offormulation per kilogram of animal.

[0039] The following are examples of various parasiticidal formulationsand methods of making these formulations that are within the scope ofthis invention. These examples are not meant in any way to limit thescope of this invention.

EXAMPLE 1

[0040] N-methyl-2-pyrrolidone was added to a vessel and warmed to 50° C.Agitation began. With continued agitation, a quantity of vitamin B₁₂amounting to 0.1% w/v of the final formulation was added to the solventand mixed with it until the vitamin B₁₂ dissolved. The resultingsolution was then cooled to room temperature. A quantity of DGMEamounting to 50% w/v of the final formulation was then added and mixedinto the solution. Next, vitamin E acetate was added in a quantityamounting to 1% w/v of the final formulation, and the resulting solutionwas mixed until all ingredients were adequately dissolved. Withcontinued agitation, a quantity of ivermectin amounting to 0.5% w/v ofthe final formulation was added and mixed into the solution untildissolved. Closantel was then added in a quantity amounting to 5% w/v ofthe final formulation, and the mixture was agitated to dissolve aportion of the closantel. With continued agitation, a supplementalamount of N-methyl-2-pyrrolidone was added in an amount sufficient tocompletely dissolve the closantel. The total amount ofN-methyl-2-pyrrolidone used made up the balance of the formulation.

EXAMPLE 2

[0041] A quantity of xylenes was added to a vessel. To the xylenes, aquantity of 2-pyrrolidone amounting to 70% w/v of the final formulationwas added and agitation began. With continued agitation, a quantity ofivermectin amounting to 0.5% w/v of the final formulation was added andmixed into the solution until dissolved. Next, closantel was added in aquantity amounting to 5% w/v of the final formulation, and the mixturewas agitated to dissolve a portion of the closantel. With continuedagitation, a supplemental amount of xylenes was added in an amountsufficient to completely dissolve the closantel. The total amount ofxylenes used made up the balance of the formulation.

EXAMPLE 3

[0042] A quantity of xylenes was added to a vessel. Agitation began.With continued agitation, a quantity of N-methyl-2-pyrrolidone amountingto 18.2% w/v of the final formulation was added. Next, a quantity of amixture of caprylic acids and esters (obtained from Croda, Inc. ofParsippany, N.J. under the tradename Crodamol Cap™) amounting to 18.2%w/v of the final formulation was added and mixed with the solution untilthe Crodamol Cap™ dissolved. Subsequently, a quantity of vitamin Eacetate amounting to 0.93% w/v of the final formulation was added. Withcontinued agitation, diethanolamine was added in a quantity amounting to0.16% w/v to the solution and mixed until dissolved. Next, a quantity ofArachis oil amounting to 16% w/v of the final formulation was added andmixed until dissolved. Following this, a quantity of ivermectinamounting to 0.45% w/v of the final formulation was added and mixed intothe solution until dissolved. Closantel was then added in a quantityamounting to 4.5% w/v, and the mixture was agitated for a timesufficient to dissolve a portion of the closantel. With continuedagitation, a supplemental amount of xylenes was added in an amountsufficient to completely dissolve the closantel. The total amount ofxylenes used made up the balance of the formulation.

EXAMPLE 4

[0043] A quantity of N-methyl-2-pyrrolidone was added to a vessel.Agitation began. With continued agitation, a quantity of isopropylalcohol amounting to 20% w/v of the final formulation was added, and thetwo solvents were mixed into solution. Next, a quantity of ethyl oleateamounting to 20% w/v of the final formulation was added, and the mixturewas agitated until all ingredients were adequately dissolved.Subsequently, a quantity of DGME amounting to 20% w/v of the finalformulation was added. Next, a quantity of benzyl benzoate amounting to20% w/v of the final formulation was added. Following this, a quantityof vitamin E acetate amounting to 1% w/v of the final formulation wasadded, and the solution mixed until all components adequately dissolved.With continued agitation, a quantity of ivermectin amounting to 0.5% w/vof the final formulation was added. Subsequently, a quantity ofclosantel amounting to 5% w/v of the final formulation was added, andthe mixture was agitated to dissolve a portion of the closantel. Withcontinued agitation, a supplemental amount of N-methyl-2-pyrrolidone wasadded in an amount sufficient to completely dissolve all of theclosantel. The total amount of N-methyl-2-pyrrolidone used made up thebalance of the formulation.

EXAMPLE 5

[0044] A quantity of N-methyl-2-pyrrolidone was added to a vessel.Agitation began. To the N-methyl-2-pyrrolidone, a quantity of benzylbenzoate amounting to 44.3% w/v of the final formulation was added, andthe mixture was agitated to ensure all ingredients dissolved. Withcontinued agitation, a quantity of ethyl oleate amounting to 30% w/v ofthe final formulation was added. Next, a quantity of ivermectinamounting to 0.5% w/v of the final formulation was added, and themixture was agitated until all of the ivermectin had dissolved. Next, aquantity of closantel amounting to 5% w/v of the final formulation wasadded, and the mixture was agitated to dissolve a portion of theclosantel. With continued agitation, a supplemental amount ofN-methyl-2-pyrrolidone was added in a quantity sufficient to dissolveall of the closantel. The total amount of N-methyl-2-pyrrolidone made upthe balance of the formulation.

EXAMPLE 6

[0045] A quantity of N-methyl-2-pyrrolidone was added to a vessel.Agitation began. With continued agitation, a quantity of a mixture ofcaprylic acids and esters (obtained from Croda, Inc. of Parsippany, N.J.under the tradename Crodamol Cap™) amounting to 18% w/v of the finalformulation was added, and the mixture was agitated to ensure that allingredient dissolved. Next, a quantity of isopropyl alcohol amounting to30% w/v of the final formulation was added and the mixture was agitateduntil all ingredients were adequately dissolved. Following this, aquantity of diethanolamine amounting to 0.05% w/v of the finalformulation was added. Next, a quantity of ivermectin amounting to 0.5%w/v of the final formulation was added and the mixture was agitateduntil all components were adequately dissolved into solution. Withcontinued agitation, a quantity of closantel amounting to 5% w/v of thefinal formulation was added, and the mixture was agitated to dissolve aportion of the closantel. With continued agitation, a supplementalamount of N-methyl-2-pyrrolidone was added in an amount sufficient tocompletely dissolve all of the closantel. The total amount ofN-methyl-2-pyrrolidone made up the balance of the formulation.

EXAMPLE 7

[0046] A quantity of propylene glycol was added to a vessel. Agitationbegan. With continued agitation, a quantity of N-methyl-2-pyrrolidoneamounting to 20% w/v of the final formulation was added. Next, aquantity of ethyl oleate amounting to 20% w/v of the final formulationwas added, and the mixture was agitated until all ingredients wereadequately dissolved. Following this, a quantity of vitamin E acetateamounting to 1% w/v of the final formulation was added. With continuedagitation, a quantity of diethanolamine amounting to 0.17% w/v of thefinal formulation was added. Next, a quantity of xylenes amounting to40% w/v of the final formulation was added. Next, a quantity ofivermectin amounting to 0.5% w/v of the final formulation was added.Next, a quantity of closantel amounting to 5% w/v of the finalformulation was added, and the mixture was agitated to dissolve aportion of the closantel. With continued agitation, a supplementalamount of propylene glycol was then added in an amount sufficient tocompletely dissolve all of the closantel. The total amount of propyleneglycol made up the balance of the formulation.

EXAMPLE 8

[0047] A quantity of N-methyl-2-pyrrolidone was added to a vessel.Agitation began. With continued agitation, a quantity of DGME amountingto 40% w/v of the final formulation was added. Next, a quantity ofpropylene glycol amounting to 10% w/v of the final formulation wasadded, and the mixture was agitated until all components were adequatelydissolved. Subsequently, a quantity of vitamin E acetate amounting to 1%w/v of the final formulation was added. With continued agitation, aquantity of a mixture of caprylic acids and esters (obtained from Croda,Inc. of Parsippany, N.J. under the tradename Crodamol Cap™) amounting to20% w/v of the final formulation was added. Next, a quantity ofdiethanolamine amounting to 0.05% w/v of the final formulation wasadded. Following this, a quantity of FD&C Blue #1 amounting to 0.02% w/vof the final formulation was added. A quantity of sterile wateramounting to 0.2% w/v of the final formulation was then added. Withcontinued agitation, a quantity of ivermectin amounting to 0.5% w/v ofthe final formulation was added. Next, a quantity of closantel amountingto 5% w/v of the final formulation was added, and the mixture wasagitated to dissolve a portion of the closantel. With continuedagitation, a supplemental amount of N-methyl-2-pyrrolidone was thenadded in an amount sufficient to completely dissolve all of theclosantel. The total amount of N-methyl-2-pyrrolidone made up thebalance of the formulation.

[0048] From the foregoing, it will be seen that this invention is onethat is well adapted to attain all the ends and objects herein above setforth together with other advantages which are obvious and inherent tothe formulation. It will be understood that certain features andsubcombinations are of utility and may be employed without reference toother features and subcombinations. This is contemplated by and iswithin the scope of the claims. Since many possible embodiments may bemade of the invention without departing from the scope thereof, it is tobe understood that all matter herein set forth is to be interpreted asillustrative and not in a limiting sense.

I claim:
 1. A parasiticidal formulation, comprising the mixture of: atleast one pyrrolidone solvent; at least one bridging solvent; and atleast one parasiticidal agent.
 2. The formulation of claim 1, whereinsaid parasiticidal agent is selected from the group consisting ofclosantel, oxyclozanide, praziquantel, pyrantels, tetrahydropyrimidines,probenzimidazoles, imidazothiazoles, macrocyclic lactones,benzimadizoles, tetramisoles, avermectins, epsiprantel, morantel,febantel, netobimin, clorsulon, bunamidine, nitroscanate, melarsomine,amidines, benzoyl urea derivatives, carbamates, nitroquanidines,pyrazoles, pyrethrins, pyrethroids, pyriproxyfen, acylhydrazones and anycombinations thereof.
 3. The formulation of claim 2, wherein saidparasiticidal agent is an avermectin selected from the group consistingof ivermectin, moxidectin, doramectin, eprinomectin, and milbemycin. 4.The formulation of claim 2, wherein said parasiticidal agent is abenzimadizole selected from the group consisting of mebendazole,oxibendazole, fenbendazole, oxfendazole, triclabendazole, flubendazole,ricobendazole, thiabendazole, and albendazole.
 5. The formulation ofclaim 2, wherein said parasiticidal agent is comprised of closantel andivermectin.
 6. The formulation of claim 5, wherein said formulationcomprises about 1-10% w/v closantel and about 0.1-5% w/v ivermectin. 7.The formulation of claim 6, wherein said formulation comprises about3-7% w/v closantel and about 0.3-0.7% w/v ivermectin.
 8. The formulationof claim 7, wherein said formulation comprises about 5% w/v closanteland about 0.5% w/v ivermectin.
 9. The formulation of claim 1, whereinsaid pyrrolidone solvent is selected from the group consisting ofN-methyl-2-pyrrolidone, 2-pyrrolidone, N,5-dimethyl-2-pyrrolidone,3,3-dimethyl-2-pyrrolidone, N-ethyl-2-pyrrolidone,N-ethoxy-2-pyrrolidone, N-ethylene-2-pyrrolidone, 1-pyrrolidone, and anycombinations thereof.
 10. The formulation of claim 9, wherein saidformulation comprises 5-90% w/v N-methyl-2-pyrrolidone.
 11. Theformulation of claim 9, wherein said formulation comprises 15-90% w/v2-pyrrolidone.
 12. The formulation of claim 1, wherein said bridgingsolvent is selected from the group consisting of diethylene glycolmonobutyl ether, benzyl benzoate, isopropyl alcohol, xylenes, and anycombinations thereof.
 13. The formulation of claim 12, wherein saidpyrrolidone solvent is 2-pyrrolidone and said bridging solvent isxylenes.
 14. The formulation of claim 12, wherein said pyrrolidonesolvent is N-methyl-2-pyrrolidone and said bridging solvent isdiethylene glycol monobutyl ether.
 15. The formulation of claim 1,wherein said mixture further comprises at least one solubility agent.16. The formulation of claim 15, wherein said solubility agent isselected from the group consisting of a mixture of caprylic acids andesters, ethyl oleate, propylene glycol, Arachis oil, and anycombinations thereof.
 17. The formulation of claim 16, wherein saidformulation comprises about 55 50% w/v solubility agent.
 18. Theformulation of claim 15, further comprising: at least one stabilizer.19. The formulation of claim 18, wherein said stabilizer is selectedfrom the group consisting of vitamin B₁₂, vitamin E acetate,niacinamide, ascorbic acid, sodium formaldehyde sulfoxylate, butylatedhydroxyaniline, thioctic acid, sorbic acid, butylated hydroxytolulene,and any combinations thereof.
 20. The formulation of claim 19, whereinsaid formulation comprises about 0.005-15% w/v stabilizer.
 21. A methodof making a parasiticidal formulation, comprising: mixing at least onepyrrolidone solvent and at least one bridging solvent to form a solventsolution; and adding at least one parasiticidal agent to said solventsolution.
 22. The method of claim 21, further comprising: adding atleast one solubility agent to said solvent solution; and adding at leastone stabilizer to said solvent solution.
 23. The method of claim 22,wherein said pyrrolidone solvent is warmed to between about 40 and 80°C., said stabilizer is mixed with said pyrrolidone solvent to form amixture, said mixture is cooled to room temperature, said bridgingsolvent is mixed with said coolted mixture to form a solvent solution,said solubility agent is mixed with said solvent solution, and saidparasiticidal agent is mixed with said solvent solution until saidparasiticidal agent is dissolved.
 24. A method for treating an animalhaving parasites, comprising: administering to said animal aparasiticidal formulation comprising a mixture of at least oneparasiticidal agent, at least one pyrrolidone solvent, and at least onebridging solvent.
 25. The method of claim 24, wherein said parasiticidalformulation is poured onto the skin of said animal and is absorbedthrough said skin.
 26. The method of claim 25, wherein said formulationis poured onto the skin of said animal in an amount of about 0.02-0.3milligrams per kilogram of animal.
 27. The method of claim 24, whereinsaid parasiticidal formulation is injected through the skin of saidanimal.